Lifespan in the nematode, C. elegans, is determined by interacting genetic pathways as well as by environmental conditions. For example, mutations in the daf-2/insulin-like signaling pathway nearly triple adult lifespan. One goal of this project is to learn why these mutants live longer. It has been shown that insulin signaling must be active in the C. elegans nervous system for normal lifespan, suggesting that neurons somehow control lifespan. One goal of this project is to identify the neurons that dictate lifespan via insulin-like signaling. A second goal of this project is to define new genes that collaborate with the insulin-like pathway. To this end, several new mutations were isolated that lengthen or shorten lifespan of long-lived insulin pathway mutants. These mutants will enable us (a) to identify the genes that are required for a long adult lifespan and (b) to identify previously unknown pathways that influence adult lifespan. Many basic biological processes are shared between nematodes and humans. Therefore, some of the genes that control lifespan in the worm may also have human versions that perform similar functions. The genes mutated in these altered-lifespan mutants are currently being mapped and cloned for molecular characterization.